Genetic effect of interleukin-1 beta (C-511T) polymorphism on the structural covariance network and white matter integrity in Alzheimer's disease.

BACKGROUND: Inflammatory processes play a pivotal role in the degenerative process of Alzheimer's disease. In humans, a biallelic (C/T) polymorphism in the promoter region (position-511) (rs16944) of the interleukin-1 beta gene has been significantly associated with differences in the secretory capacity of interleukin-1 beta. In this study, we investigated whether this functional polymorphism mediates the brain networks in patients with Alzheimer's disease. METHODS: We enrolled a total of 135 patients with Alzheimer's disease (65 males, 70 females), and investigated their gray matter structural covariance networks using 3D T1 magnetic resonance imaging and their white matter macro-structural integrities using fractional anisotropy. The patients were classified into two genotype groups: C-carriers (n = 108) and TT-carriers (n = 27), and the structural covariance networks were constructed using seed-based analysis focusing on the default mode network medial temporal or dorsal medial subsystem, salience network and executive control network. Neurobehavioral scores were used as the major outcome factors for clinical correlations. RESULTS: There were no differences between the two genotype groups in the cognitive test scores, seed, or peak cluster volumes and white matter fractional anisotropy. The covariance strength showing C-carriers > TT-carriers was the entorhinal-cingulum axis. There were two peak clusters (Brodmann 6 and 10) in the salience network and four peak clusters (superior prefrontal, precentral, fusiform, and temporal) in the executive control network that showed C-carriers < TT-carriers in covariance strength. The salience network and executive control network peak clusters in the TT group and the default mode network peak clusters in the C-carriers strongly predicted the cognitive test scores. CONCLUSIONS: Interleukin-1 beta C-511 T polymorphism modulates the structural covariance strength on the anterior brain network and entorhinal-interconnected network which were independent of the white matter tract integrity. Depending on the specific C-511 T genotype, different network clusters could predict the cognitive tests.

Elevated basal cortisol level predicts lower hippocampal volume and cognitive decline in Alzheimer's disease.

Elevated glucocorticoid concentrations, decreased hippocampal volume and frontal atrophy with poor cognitive function have been reported in the elderly but not extensively in Alzheimer's disease (AD). We enrolled 172 patients with AD over a 2-year follow-up period. Basal cortisol levels, biochemistry tests and mini-mental state examination (MMSE) scores were obtained and hippocampal and frontal atrophy were measured by CT scan for correlation. Basal plasma cortisol levels increased with age. Further, basal plasma cortisol levels were correlated with the radial width of the temporal horn, and elevated levels of plasma cortisol predicted a worse general cognitive performance. Higher plasma cortisol levels also correlated with rapid declines in MMSE scores after 2 years. Bilateral frontal atrophy showed no correlation with the above parameters. The relationship between high cortisol levels and hippocampal atrophy might adversely affect AD patients disproportionately, either in anatomical or cognitive function.